Indolic alkaloids are among the natural compounds which comprise a vast series of derivatives, some of which show very interesting pharmacological activity and properties, especially as regards the treatment of tumours or neoplastic pathologies in general. In particular, among the indolic alkaloids with these properties, phidianidine B is a natural molecule recently isolated together with the brominated derivative, phidianidine A, from the opisthobranch mollusk Phidiana militaris (Carbone et al., Organic Letters, 2011, 13(10), 2516-2519), collected in the South China Sea.

Phidianidines are indolic alkaloids characterized by a 1,2,4-oxadiazol nucleus, a structural element never found in natural marine molecules, and they show an interesting, highly selective anti-proliferative activity on tumour cell lines at extremely low concentrations (nanomolar). In particular, phidianidine B has a high cytotoxic activity against the HeLa cell line (uterine cervix cancer).
Although the 1,2,4-oxadiazol nucleus is extremely rare in nature, there is enormous interest in synthesizing compounds containing this scaffold, since they are extensively used in medicinal chemistry programs as pro-drugs, being metabolically stable and bioavailable compounds. In the literature numerous syntheses of 1,2,4-oxadiazol nuclei have been described (e.g. Pace & Pierro, Org. Biomol. Chem., 2009, 7, 4337-4348 and cited references; Coté et al., Tetrahedron Lett., 2011, 52, 5750-5751; Nishiwaki et al., Org. Biomol. Chem., 2011, 9, 6750-6754; Sanchit et al., IJRAP, 2011, 2, 459-468).
The majority of the syntheses reported use two principal methods (Scheme A):    1) dipolar 1,3 cycloaddition of nitriles to nitrile oxides;    2) cyclization of amidoxime derivatives.

As said above, phidianidine A and B are isolated from a particular type of marine mollusk, which does not, however, enable large quantities of active ingredient to be obtained. It should be noted that the possibility of obtaining natural molecules with high pharmacological potential by chemical synthesis in the laboratory is without a doubt fundamental for gaining access to the high quantities of compound that are necessary for developing studies on biological activity.
The Applicant has found a new process for the preparation of a series of natural indolic alkaloid derivatives which, advantageously, enables the isolation of the products thereby obtained also in large quantities (in the order of tens of grams). The present process, in fact, comprises the preparation of a 1,2,4-oxadiazol key intermediate which, given its versatility, can be used to obtain a series of derivatives with potential antitumoural activity, including phidianidine A and B.
Moreover, the reaction for forming the 1,2,4-oxadiazol nucleus according to the present invention is carried out using an amidoxime, in particular a hydroxyguanidine, already containing the protected functional alkylamine group (4). In such a manner it is possible to avoid the problems connected to the subsequent introduction of the alkyl residue on a substrate containing two competing sites (indole NH and oxadiazole NH) as described in the literature.